Sexual Function and Fertility in Adult Females and Males with Congenital Adrenal Hyperplasia

Abstract

Female patients with classic 21-hydroxylase deficiency (21-OHD) present with decreased fertility and low childbirth rates, women with a salt-wasting form of 21-OHD being most severely affected. In cases of undersubstitution with glucocorticoids, tonic androgen secretion disturbs ovulation. However, even adequately substituted females may present with apparent infertility. Despite adrenal androgen suppression, adrenal progesterone secretion can prevent thickening of the endometrium in the follicular phase. Furthermore, functional ovarian hyperandrogenism is a common finding even in women with well-controlled classic 21-OHD. Psychosexual factors may also contribute significantly to decreased childbirth rates found in these patients. Genital ambiguity may lead to a disturbed body image and the patients have been found to feel less feminine than healthy control women. The repeated psychological insult caused by frequent genital examinations and operations is also important, though its exact impact has been difficult to determine. Finally, prenatal androgen excess can cause masculinization of the central nervous system leading to boyish behavior in childhood and decreased heterosexual activity in adulthood. Some recent reports show a high rate of infertility also in men with 21-OHD. They are at risk of benign testicular tumors, adrenal rests, which can lead to permanent infertility. Also, raised adrenal androgen production leading to increased estrogen concentrations can suppress gonadotropin secretion and may lead to a hypogonadotropic state.

Non-classical 21-hydroxylase deficiency: prevalence in males with unexplained abnormal sperm analysis

“…Yet in the small cohort studies of males with C-21-OHD who have markedly increased adrenal androgen levels (19)(20)(21)(22), infertility was limited to those with testicular adrenal rests. In addition, a small Finnish study reported that males with 21-OHD had similar levels of gonadotropins and inhibin B to age-matched controls (22).…”

“…Studies of males treated with large doses of exogenous testosterone combined with progesterone have reported findings of suppressed gonadotropin levels and spermatogenesis and consequent oligospermia (18). Accordingly, it has been speculated that the infertility associated with untreated CAH in men might be attributable to overproduction of adrenal androgens, leading to suppressed gonadotropin secretion and a hypogonadotropic state (19). However, the reported data on fertility in males with CAH are conflicting (20)(21)(22).…”

Comparison of Multiple Steroid Concentrations in Serum and Dried Blood Spots throughout the Day of Patients with Congenital Adrenal Hyperplasia

“…Current replacement treatment (glucocorticoids) does not precisely replicate the circadian rhythm of cortisol secretion because it lacks the close temporal relationship to adrenocorticotropin (ACTH) pulses, and increased adrenal activity will continue despite treatment. Increasing treatment doses to achieve satisfactory androgen suppression exposes the patient to the negative effects glucocorticoids have on growth, explaining why some ‘well-controlled’ CAH patients may experience early puberty, compromised final height, polycystic ovarian disease, and male infertility [4,5]. …”

Intersexuality and Alternative Gender Categories in Non-Western Cultures

“…From the beginning of the 20th century, intersexuality has been recognized by modern Western medicine as a medical condition, a disorder of sex development, requiring life-long medical treatment, with genital abnormalities being corrected by surgery to allow so-called normal sexual function [1]. Corrective genital surgery is guided by cosmetic appearance and sexual functionality of the external genitalia, but often does not allow local sexual sensations and feelings [2,3,4,5]. Certain advocacy groups even complain that Western society would force individuals with disorders of sex development to conceal their status and make them choose either a male or female role, whereas other (non-Western) societies consider their condition special, and give them a special gender role often associated with high social status [6, 7].…”